title: Nonviral retrograde gene transfer of human hepatocyte growth factor improves neuropathic pain-related phenomena in rats.
abstract: Peripheral nerve injury occasionally causes chronic neuropathic pain with hyperalgesia and allodynia. However, its treatment is difficult. Here, we used a chronic constriction injury (CCI) model in rats to investigate the effects on experimental neuropathic pain of the human hepatocyte growth factor (HGF) gene delivered into the nervous system by retrograde axonal transport following its repeated intramuscular transfer, using liposomes containing the hemagglutinating virus of Japan (HVJ). CCI (control) rats exhibited marked mechanical allodynia and thermal hyperalgesia, and decreased blood flow in sciatic nerve and hind paw. All these changes were significantly reversed by HGF gene transfer. In the sciatic nerve in HGF-treated rats, the size-frequency distributions for myelinated and unmyelinated axons each showed a rightward shift, the number of myelinated axons >5 microm in diameter was significantly increased, and the mean diameter of unmyelinated axons was significantly increased (versus CCI rats). Levels of P2X3, P2X4, and P2Y1 receptor mRNAs, and of interleukin-6 (IL-6) and activating transcription factor 3 (ATF3) mRNAs, were elevated in the ipsilateral dorsal root ganglia and/or sciatic nerve by CCI, and these levels were decreased by HGF gene transfer. These results may point toward a potential new treatment strategy for chronic neuropathic pain in this model.
authors.affiliation: Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Tsuchihara
authors.forename: Sho
authors.initials: S
authors.lastname: Ogata
authors.forename: Koichi
authors.initials: K
authors.lastname: Nemoto
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Kato
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Maki
authors.initials: M
authors.lastname: Uenoyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzuki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Amako
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arino
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics; D000818:Animals; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015850:Interleukin-6 / Q000235:genetics; D008081:Liposomes; D008297:Male; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D029082:Sendai virus / Q000235:genetics
chemical_list: D051700:Activating Transcription Factor 3; C066855:HGF protein, human; D015850:Interleukin-6; D008081:Liposomes; D017228:Hepatocyte Growth Factor